St. John’s Wort

Study findings are variable, but SJW may benefit patients with mild-to-moderate depression who have no suicidal ideation. Well-designed studies have been done on SJW treating major depression. Recommended formulations include preparations standardized to 0.2 to 0.3% hypericin, to 1 to 4% hyperforin, or to both (usually).

St. John’s wort is also said to be useful for treating HIV infection because hypericin inhibits a variety of encapsulated viruses, including HIV, but has proven adverse interactions with protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs) and should therefore be avoided (1, 2).

SJW has also been claimed to treat skin disorders (including psoriasis), as well as attention-deficit/hyperactivity disorder (ADHD) in children. It is also credited with reducing menopausal symptoms.

Numerous randomized, placebo-controlled studies have evaluated safety and efficacy of SJW in treating mild-to-moderate depression and, recently, major depressive disorders (3–8). SJW has also been compared with tricyclic antidepressants (amitryptiline, imipramine) and more recently with the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine (). SJW has also been compared with tricyclic antidepressants (amitryptiline, imipramine) and more recently with the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine (4–8). Most placebo-controlled studies have shown that standardized extracts of SJW in the dose range of 300 mg to 900 mg once a day are moderately effective in the treatment of mild-to-moderate depressive symptoms. Some studies have shown equivalence of 900 mg of SJW to low-dose imipramine and low-dose fluoxetine. A study of patients with major depression failed to show significant improvement over either placebo or standard doses of sertraline over a short period of time (). Most placebo-controlled studies have shown that standardized extracts of SJW in the dose range of 300 mg to 900 mg once a day are moderately effective in the treatment of mild-to-moderate depressive symptoms. Some studies have shown equivalence of 900 mg of SJW to low-dose imipramine and low-dose fluoxetine. A study of patients with major depression failed to show significant improvement over either placebo or standard doses of sertraline over a short period of time (7). However, the authors state that both SJW and sertraline were equally effective over long periods of time, indicating the potential alternative economic value of SJW as a therapeutic treatment of depression when taken at low doses and when drug interactions are not of concern (). However, the authors state that both SJW and sertraline were equally effective over long periods of time, indicating the potential alternative economic value of SJW as a therapeutic treatment of depression when taken at low doses and when drug interactions are not of concern (7).

Overall, some studies show efficacy of SJW in treating mild depression, whereas in major depression most studies do not show efficacy. Differences in study design (lack of active control and placebo), study populations (major vs mild/moderate depression), length of time, and dosing of SJW or comparator agents are likely responsible for some variance in results.

A 2016 systematic review of 35 studies (6993 subjects) compared SJW to placebo or conventional antidepressants (9). SJW was superior to placebo but not different than conventional antidepressants for mild-to-moderate depression. However, studies were heterogenous and severe depression was not studied (9). A 2017 meta-analysis of 27 studies (3808 subjects) compared SJW to SSRIs. SJW was comparable to SSRIs in response and remission for mild-to-moderate depression but had lower discontinuation rates (10).

Clinical guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce have stated that St. John's wort monotherapy may be used for mild to moderate unipolar depression (Clinical guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce have stated that St. John's wort monotherapy may be used for mild to moderate unipolar depression (11).

A meta-analysis of 6 trials including 717 menopausal women evaluated SJW monotherapy or in combination with either black cohosh or chasteberry versus placebo to treat menopausal symptoms. Although the authors concluded that SJW or its combination with other phytotherapies may help with menopausal symptoms they noted great heterogeneity in the evaluated studies and recommended further research (A meta-analysis of 6 trials including 717 menopausal women evaluated SJW monotherapy or in combination with either black cohosh or chasteberry versus placebo to treat menopausal symptoms. Although the authors concluded that SJW or its combination with other phytotherapies may help with menopausal symptoms they noted great heterogeneity in the evaluated studies and recommended further research (12). A randomized trial in 80 postmenopausal women with mild depression demonstrated some benefit for not only menopausal symptoms but also depression (13).

Two small pilot studies show potential improvement in skin lesions with topical application of hypericin when used for skin disorders (eg, psoriasis) (14, 15). Another small trial showed SJW (standardized to hypericin but not hyperforin) did not relieve symptoms of attention-deficit/hyperactivity disorder (ADHD) in children (16).

Photosensitivity, dry mouth, constipation, dizziness, confusion, and mania (in patients with bipolar disorder) may occur. A rare case of supraventricular tachycardia was reported (17). SJW should not be used by pregnant and lactating women.

Potential adverse interactions occur with cyclosporine, digoxin, iron supplements, monoamine oxidase inhibitors (MAOIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), oral contraceptives, opioids, protease inhibitors, SSRIs, tricyclic antidepressants, and warfarin, as well as some direct-acting oral anticoagulants (Potential adverse interactions occur with cyclosporine, digoxin, iron supplements, monoamine oxidase inhibitors (MAOIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), oral contraceptives, opioids, protease inhibitors, SSRIs, tricyclic antidepressants, and warfarin, as well as some direct-acting oral anticoagulants (18–20). (See also table Some Possible Dietary Supplement–Medication Interactions.)

1. 1. Maury W, Price JP, Brindley MA, et al. Identification of light-independent inhibition of human immunodeficiency virus-1 infection through bioguided fractionation of Hypericum perforatum. Virol J. 6:101-113, 2009. doi:10.1186/1743-422X-6-101

2. 2. Kakuda TN, Schöller-Gyüre M, Hoetelmans RM. Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet. 50(1):25-39, 2011. doi: 10.2165/11534740-000000000-00000

3. 3. Solomon D, Adams J, Graves N. Economic evaluation of St. John's wort (. Economic evaluation of St. John's wort (Hypericum perforatum) for the treatment of mild to moderate depression. J Affect Disord. 148(2-3):228-234, 2013. doi: 10.1016/j.jad.2012.11.064

4. 4. van Gurp G, Meterissian GB, Haiek LN, et al. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician. 48:905-912, 2002

5. 5. Woelk H. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. BMJ. 321(7260):536-539, 2000. doi: 10.1136/bmj.321.7260.536

6. 6. Fava M, Alpert J, Nierenberg AA, et al. A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol. 25(5):441-447, 2005. doi:10.1097/01.jcp.0000178416.60426.29

7. 7. Sarris J, Fava M, Schweitzer I, et al. St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT. Pharmacopsychiatry. 45(7):275-278, 2012. doi: 10.1055/s-0032-1306348

8. 8. Seifritz E, Hatzinger M, Holsboer-Trachsler E. Efficacy of Hypericum extract WS(R) 5570 compared with paroxetine in patients with a moderate major depressive episode - a subgroup analysis. Int J Psychiatry Clin Pract. 20(3):126-32, 2016. doi: 10.1080/13651501.2016.1179765

9. 9. Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John's wort for major depressive disorder. . A systematic review of St. John's wort for major depressive disorder.Systematic Reviews. 5:148, 2016. doi: 10.1186/s13643-016-0325-2

10. 10. Ng QX, Venkatanarayanan N, Ho CY. Clinical use of Hypericum perforatum (St John's wort) in depression: a meta-analysis. J Affect Disord. 210:211-221, 2017. doi: 10.1016/j.jad.2016.12.048

11. 11. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. World J Biol Psychiatry. 2022 Jul;23(6):424-455. doi: 10.1080/15622975.2021.2013041

12. 12. Liu YR, Jiang YL, Huang RQ, Yang JY, Xiao BK, Dong JX. Hypericum perforatum L. preparations for menopause: a meta-analysis of efficacy and safety. Climacteric. 2014 Aug;17(4):325-35. doi: 10.3109/13697137.2013.861814

13. 13. Eatemadnia A, Ansari S, Abedi P, Najar S. The effect of Hypericum perforatum on postmenopausal symptoms and depression: A randomized controlled trial. Complement Ther Med. 2019 Aug;45:109-113. doi: 10.1016/j.ctim.2019.05.028. Epub 2019 May 31. PMID: 31331546.

14. 14. Najafizadeh P, Hashemian F, Mansouri P, et al. The evaluation of the clinical effect of topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: a pilot study. Australas J. 53(2):131-135, 2012. doi: 10.1111/j.1440-0960.2012.00877.x

15. 15. Rook AH, Wood GS, Duvic M, et al. A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis. J Am Acad Dermatol. 63(6):984-990, 2010. doi: 10.1016/j.jaad.2010.02.039

16. 16. Weber W, Vander Stoep A, McCarty RL, et al:. Hypericum perforatum (St John's wort) for attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled trial. JAMA. 299(22):633-2641, 2008. doi: 10.1001/jama.299.22.2633

17. 17. Fisher KA, Patel P, Abualula S, Concepion L. St. John's wort-induced supraventricular tachycardia. . St. John's wort-induced supraventricular tachycardia.Cureus. 13(4):e14356, 2021. doi:10.7759/cureus.14356

18. 18. Borrelli F, Izzo AA. Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS J. 11(4):710-727, 2009. doi: 10.1208/s12248-009-9146-8

19. 19. Nadkarni A, Oldham MA, Howard M, et al. Drug-drug interactions between warfarin and psychotropics: updated review of the literature. Pharmacotherapy. 32(10):932-942. 2012. doi: 10.1002/j.1875-9114.2012.01119

20. 20. Tsai HH, Lin HW, Simon Pickard A, et al. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract. 66(11):1056-1078, 2012. doi: 10.1111/j.1742-1241.2012.03008.x

The following English-language resource may be useful. Please note that The Manual is not responsible for the content of this resource.

1. National Institutes of Health (NIH), National Center for Complementary and Integrative Health: St. John’s Wort